KR102234207B1 - Reaction culture device, immune analyzer and reaction culture method - Google Patents

Abstract

The present invention relates to a reaction culture apparatus, an immunological analyzer, and a reaction culture method, wherein the reaction culture apparatus comprises: a reaction unit 10 for cultivation equipped with a reaction vessel; And a mobile unit (20) for carrying in or out of the reaction vessel into the reaction unit (10); The reaction unit 10 includes a rotation device 11, a culture position is installed on the rotation device 11, and the culture position is at intervals of a predetermined time (T) according to the rotation device 11 Rotated by a predetermined angle [theta]; The mobile unit 20 may take out the reaction vessel from the culture position according to the _{culture time (t 1 ).} In the present invention, freely controllable and variable incubation time can be implemented simply and efficiently, and the control that exists to implement variable incubation time in the prior art is complex, low reliability, and difficult to execute high-speed automation. Solve the problem effectively.

Description

Reaction culture device, immune analyzer and reaction culture method

The present invention relates to the field of in vitro diagnostic devices, and in particular, to a reaction culture device, an immune analyzer, an automatic analysis device, and a reaction culture method thereof.

) 및 자가 면역 질환의 진단에 사용된다.Autoimmune analysis is based on an immune reaction in which antigen and antibody bind to each other, and is used as a marker for antigen and antibody using enzymes, lanthanide elements or chemiluminescent agents, and through a series of amplification chain reactions, optical signals or electrical signals Correlates to the analyte concentration, etc. to analyze the antigen or antibody to be measured in a human sample, and is mainly used in hospital examinations, external independent laboratories, and institutions such as blood measurement centers, and quantitative and semi-quantitative for each analyte in human body fluids. , Or by performing qualitative measurement, infectious disease, tumor, endocrine function, cardiovascular disease, bovine beef (

) And in the diagnosis of autoimmune diseases.

1 and 2, the immunoassay generally includes a one-step method, a delayed one-step method, a two-step method, and the like, depending on the measurement principle and mode. The main measurement steps typically include sample and reagent addition, reactant mixing, incubation, wash separation (Bound-Free, abbreviated B/F), addition of signal reagents, measurement, and the like. The culture of the present invention is a process in which an antigen-antibody binding reaction or an avidin-biotin binding reaction occurs in a constant temperature environment of the reaction unit, in particular, the reaction material in the reaction vessel before washing and separation. , One-time incubation by the one-step method, that is, is to perform one-time culture before washing separation; The two cultures by the delayed one-step method include the first culture before the addition of the second reagent and the second culture before washing and separation; The two-time culture by the two-step method includes the primary culture before the primary washing separation and the secondary culture before the secondary washing separation. A detailed description of the measurement steps according to the different measurement modes is as follows.

1) One-step method: Referring to Fig. 1, sample (S) and reagent (R) are added, mixed uniformly (mixing is not necessary in some measurement methods, and will not be described again later), and culture is performed. , After completion, wash separation is performed, then signal incubation is performed by adding a signal reagent, and finally measurement. In particular, since the specific components of the signal reagent are different, the signal culture is not necessary in some light emitting systems, and thus, measurement can be performed during the addition of the signal reagent or immediately after the addition of the signal reagent.

2) Delayed one-step method: The difference from the one-step method is that the reagent is added in two portions, the first reagent is added and mixed, and then the first cultivation is performed, and after the first cultivation is completed, the second reagent is added and mixed evenly. It is to do. Compared with the one-step method, the cultivation, reagent addition, and mixing operation are included once more, and the remaining process is the same as the one-step method.

3) Two-step method: The difference from the delayed one-step method is that it includes one more washing and separating step, and the remaining steps are the same.

In the cultivation step of the above process, the existing specific technical solutions are generally divided into two methods: fixed time cultivation and variable time cultivation. In the fixed-time culture method, all measurement incubation times in each measurement mode are the same, for example, measurements by all one-step methods can only be performed for 20 minutes, and measurements by all two-step methods are performed for 10 minutes. Only the primary culture and the secondary culture for 10 minutes can be performed, and due to the difference in specific measurement items depending on the reagent material, formulation, production process, reaction principle and conditions, the fixed-time culture is performed in the actual development and measurement process. It is difficult to increase the difficulty of reagent development or to guarantee measurement performance such as sensitivity, and it is difficult to satisfy all of a plurality of different measurement items. The fixed-time culture method is prepared for constraints and limitations on drug development and performance, while the variable-time culture method is highly versatile and adaptable, and the incubation time can be freely installed according to each different measurement item, i.e., each measurement item has its own As the most suitable incubation time can be selected, the restriction of reagent development can be reduced and the performance of the reagent can be maximized. In order to perform variable-time cultivation, a conventional technical solution generally uses an independent culture tray that can only perform culture, and the culture tray requires rotation and stopping several times in one measurement cycle, and the angle of rotation each time. Since is determined according to the incubation time, the technical solution has disadvantages that control is complicated, it is difficult to implement the technology, and is not suitable for high-speed automatic measurement.

In view of this, the present invention has a simple and reliable control, a more free and efficient reaction culture apparatus in which culture processes and methods are free, and an immune analyzer equipped with the same, in order to solve the disadvantages and problems that are commonly present in the prior art. It provides a reaction culture method.

According to an aspect of the present invention, there is provided a reaction cultivation apparatus comprising a reaction unit for cultivation in which a reaction vessel is mounted, a mobile unit for carrying the reaction vessel into or out of the reaction unit, wherein the reaction unit is It includes a rotating device, the cultivation position is installed on the rotating device, the cultivation position is rotated by a predetermined angle (θ) at intervals of a predetermined time (T) by the rotating device to move forward; The rotating unit removes the reaction vessel from the culture position according to the _{incubation time (t 1 ).}

According to another aspect of the present invention, an immunoassay is provided, and the reaction culture device is mounted on the immunoassay.

According to another aspect of the present invention, in the reaction culture method, the carrying step of transferring the reaction vessel containing the reactant by the mobile unit to the culture position of the reaction unit; In the culture position, the reaction vessel is rotated by a predetermined angle (θ) at intervals of a predetermined time (T) by a rotating device, and incubated for a variable incubation time [t ₁ =(Ω/θ)T], where Ω is a reaction A culturing step, wherein the vessel is the total angle rotated by the rotating device in the culture position, and Ω is an integer multiple of θ; After the incubation time (t ₁ ) has elapsed, the mobile unit provides a reaction culture method including a carrying out step of removing the reaction vessel from the culture position of the reaction unit.

The reaction culture apparatus of the present invention moves the reaction vessel by a predetermined angle (θ) at intervals of a predetermined time (T), and the moving unit unloads the reaction vessel from the culture position according to the _{variable culture time (t 1 ).} In the present invention, in addition to implementing freely variable incubation time, it is possible to control simply and efficiently, washing, separating and/or measuring simultaneously on the reaction culture device, so that the immunoassay is simple, reliable, compact and cost-saving. This effectively solves the problems of the prior art in which the control for implementing a variable incubation time is complicated, the reliability is low, high-speed automation is difficult to execute, and the washing, separation and/or measurement cannot be performed simultaneously. do.

1 is a diagram showing a reaction mode different from the one-step method.
2 is a diagram showing a response mode according to a delayed one-step method and a two-step method.
3 is a diagram showing a first embodiment of the reaction culture apparatus of the present invention.
4 is a view showing the operation timing of the reaction tray of the present invention.
5 is a view showing the cultivation step of the present invention.
6 is a view showing a second embodiment of the reaction culture apparatus of the present invention.
7 is a diagram showing a third embodiment of the reaction culture apparatus of the present invention.

Hereinafter, the present invention will be described in detail with reference to the accompanying drawings and specific embodiments.

In one aspect, the reaction culture apparatus according to the present invention includes a reaction unit for cultivation equipped with a reaction vessel; And a moving unit for carrying in or out of the reaction vessel into or out of the reaction unit, the reaction unit includes a rotating device, a culture position is installed on the rotating device, and the culture position is set by the rotating device for a predetermined time ( It is rotated by a predetermined angle [theta] at intervals T) and moves forward; The mobile unit may remove the reaction vessel from the culture position according to the _{incubation time (t 1 ).}

3, a first embodiment of the reaction culture apparatus of the present invention is presented. The reaction culture device 100 mainly includes a reaction unit 10 (including a rotating device and a warming device), a moving unit 20, and the like. The functions and roles of each part will be described below.

The reaction unit 10 mounts and cultures a reaction vessel containing a reactant. The reaction unit 10 mainly includes a warming device and a rotating device. The outer side of the warming device is formed of an insulating material such as a heat insulating fiber, and a heating device and a sensor may be mounted on the inside of the side or the bottom, and the upper side has a structure such as a cover plate, etc., for the reaction unit. While providing an incubation environment, it is possible to prevent or reduce heat loss of the reaction unit. Of course, in order to improve the heat transfer efficiency, the heating device may be mounted on the rotating device. It is preferable that the rotating device is one, and includes a driving unit, an electric mechanism, and a related control circuit, and the rotating device rotates at a certain angle θ at a certain time interval (for example, one cycle or period T). By controlling and driving, the reaction vessel is moved forward by a certain distance (for example, one reaction vessel position is moved). On a rotating device, a reaction vessel, a plurality of independent holes, grooves, brackets, bases, or other structures suitable for mounting the reaction vessel are provided, and this is defined as the reaction vessel position. In this embodiment, the warming device of the reaction unit 10 is a pot body 12 and an upper cover (not shown), and the rotating device is one reaction tray 11. The reaction tray 11 can be rotated about a central axis, and four cycles of reaction vessel positions (11a, 11b, 11c, 11d) each having a rotational center centrifuged thereon are installed, and the number of cycles is 1, for example. It can be set to one, two, three or more, and a plurality of reaction vessel positions are provided on each cycle, and the quantity of reaction vessel positions in each cycle may be the same or different. In this example, 30 reaction vessel positions are provided on each cycle each, and the reaction vessel positions of the four cycles are all culture spots, and are configured to receive and cultivate the reaction vessels containing the reactants. In order for the position of any one reaction vessel on the rotating device to indicate the physical position at a specific point in time, an absolute coordinate system is installed, and the position number is set to increase to 1, 2, 3 ... 30 along the counterclockwise direction in the coordinate system. .

The moving unit 20 moves the reaction vessel along different positions in the reaction culture device 100. The moving unit can be any suitable mechanism for transferring or moving the reaction vessel, and the preferred moving unit of the present invention mainly includes structures such as a drive mechanism, a horizontal robot arm, a grip and release mechanism, and the like. The grip and release mechanism is generally a mechanical finger capable of holding or lowering the reaction vessel, and the horizontal moving robot arm is a driving mechanism to control the grip and release mechanism in the X-direction, Y-direction, X-direction and Y-direction, and radial direction. , By moving the grip and release mechanism in a circumferential direction, a radial direction and a circumferential direction, etc., to transfer the reaction vessel gripped by the grip and release mechanism to different positions. In addition to the horizontal movement, the movement unit 20 can be moved up and down to convey the reaction vessel to a different position or take it out from another position. Depending on the measuring side speed and the overall device configuration, one or more mobile units can be installed. In this embodiment, the moving unit 20 can perform a three-dimensional movement as one, whereby the entire device can be configured to be more compact and cost can be reduced. The moving unit 20 includes an X-direction moving robot arm 20a, a Y-direction moving robot arm 20b, a Y-direction rail 20c, and a vertical moving mechanism, a mechanical finger (not shown), and the like. The moving unit 20 can simultaneously move the mechanical fingers horizontally along the X and Y directions, and the horizontal movement range falls within the square 26 which is the rim, that is, all reaction vessel positions on the reaction tray 11 ( Since the culture position) falls within the horizontal movement range of the mobile unit 20, the mobile unit 20 freely controls the cultivation time by bringing the reaction vessel into a different rebound position or taking it out from a different reaction position.

The reaction tray 11 has a predetermined angle θ at intervals of a predetermined time T (in this embodiment, T is 24 seconds, and one measurement experiment cycle) (in this embodiment, θ is 12°) Rotate as many times, and can be rotated counterclockwise or clockwise. For example, it rotates by 12° counterclockwise at intervals of 24 seconds, and advances one reaction vessel position. Refer to FIG. 4 for the order of operation time of the reaction tray, Tm and Tn represent the m-th measurement cycle and the n-th measurement cycle, respectively, and the reaction tray 11 rotates and advances during the time zone C5-T, and stops at other time zones. Is in a state. While the reaction tray 11 is stopped after rotation, the moving unit 20 carries the reaction vessel 20 into the culture position of the reaction tray 11 or removes it from the culture position. The transfer unit 20 uses C ₁ -C ₂ hours to transfer the reaction vessel to the cultivation position, and C ₃ -C ₄ hours to move the reaction vessel from the cultivation position. In this example, C ₀ =C ₂ -C ₁ =0.2 minutes, which is the time difference in which the reaction vessel is carried into and out of the culture position on the reaction tray within one measurement period, and is usually a fixed constant. Any reaction vessel containing the reactants is placed in a position of any reaction vessel on the reaction tray for _{C 1} -C ₂ hours in the Tm cycle, and removed from the reaction vessel position during the _{time C 3} -C _{4 in the nth measurement cycle Tn.} If so, the incubation time (t ₁ ) is (Ω/θ)T+C ₀ =((mn)θ/θ)T+C ₀ =(mn)T+C ₀ .

Hereinafter, with reference to FIGS. 3 to 5, as an example of a one-step measurement for 5 minutes incubation, the reaction culture process and steps of the reaction culture apparatus 100 will be briefly described.

Step 200 is the step of bringing the reaction vessel into the culture position by the mobile unit. During the stop time (C ₁ -C ₂ hours) at which the reaction tray 11 stops rotating, the moving unit 20 moves the reaction vessel containing the reactants to the incubation position on the absolute position (1), and selects any of the four cycles. It should be located on one of the above. For example, it is possible to select the culture position on the outer cycle 11d at the absolute position 1.

Step 201 is a step of incubating the reaction vessel for t _{1 hour.} The reaction vessel is rotated counterclockwise by a predetermined angle (θ) of 12° every 24 seconds in one cycle (T) by the reaction tray 11, and moves forward by one reaction vessel position. After passing through 12 cycles T, the reaction vessel is rotated by a total angle (Ω) 144° by a rotating device in the culture position to be positioned on the absolute position 13, and the incubation time (t ₁ ) accordingly is ( Ω/θ)T+C ₀ =4.8+0.2=5min. In this example, the constant C ₀ is 0.2 minutes.

Step 202 is a step of unloading the reaction vessel to the culture position by the mobile unit. After the incubation time (t ₁ ), the mobile unit 20 is in the culture position on the outer cycle 11d located at the absolute position 13 within the _{stop time (C 3} -C _{4 hours) at which the reaction tray 11 stops rotating.} The reaction vessel containing the reactants was taken out.

For delayed one-step and two-step methods requiring two cultures, it will be understood by those skilled in the art that the incubation time of this example can be varied according to a similar process and method.

As can be seen from the above, in this embodiment, the variable incubation time (t ₁ ) that can be performed in the culture position is (Ω/θ)T+C ₀ , where Ω is the rotation device in which the reaction vessel is in the culture position. Is the total angle at which the reaction vessel is rotated, Ω is an integer multiple of θ, and C ₀ is a constant less than or equal to T. In particular, in this embodiment, for a longer incubation time, the total angle Ω in which the reaction vessel is rotated according to the rotating device in the incubation position on the reaction tray includes a value greater than 360°. In other words, the variable incubation time (t ₁ ) includes a value greater than (360°/θ)T. Therefore, the reaction vessel moves forward while rotating by the reaction tray on the culture position, and the mobile unit can freely change the incubation time by bringing the reaction vessel into the culture position on the reaction tray or taking it out from the culture position at different positions. .

As can be seen from the above, in this embodiment, the reaction tray is rotated by a predetermined angle at intervals of a predetermined time to move the culture position located thereon to a different position, and the horizontal movement range of the moving unit is on the reaction tray. All incubation positions can be covered, and the reaction vessel can be moved to different incubation positions. Through the arrangement and cooperation of the moving unit and the reaction tray, the incubation time can be freely controlled, and the reaction tray existing in the prior art avoids a situation in which the rotation is stopped several times during one cycle and the rotation angle is uncertain each time, The difficulty and complexity of control can be reduced, and the measurement efficiency of the entire device can be improved.

6 shows Example 2. In the second embodiment according to the present invention, in contrast to the second embodiment, the main difference is that the washing and separating device 30 and the measuring device 40 are further installed on the reaction culture device 100. In addition, in Example 1, the reaction vessel positions of the four cycles of the reaction unit are all culture positions, and in this example, only the reaction vessel positions of the three cycles located on the inside are the culture positions, mainly implementing the culture function, and In the reaction vessel position, mainly the washing, separation and measurement functions are implemented. At this time, in the reaction vessel position of the outer cycle, the culture function may be partially implemented in the process of moving the reaction vessel to the washing, separating and measuring device. In addition to providing a culture environment, the warming device of the present embodiment can support and fix the magnetic field generating device of the washing/separating device 30, thereby providing a magnetic field environment to the washing/separating device. The thermal insulation device not only provides the mounting position of the measuring device 40, but can also provide a dark room environment in which the measuring device 40 is required. The cleaning and separating device of the present invention includes a magnetic field generating device and a cleaning mechanism. The magnetic field generating device provides a magnetic field environment to adsorb paramagnetic particles in the reaction vessel to the inner wall of the reaction vessel. Due to factors such as response time, moving distance, and resistance of the magnetic field, it takes a certain amount of time for paramagnetic particles to be adsorbed on the inner wall of the reaction vessel, and it usually takes several to tens of seconds, and waste liquid (including unbound components) can be introduced. Each time, the reaction vessel passes through the magnetic field for a certain amount of time. The preferred magnetic field generating device of the present invention can be mounted or fixed directly to the warming device of the reaction unit, thereby reducing the cost by eliminating the need for a separate fixing mechanism, and placing the magnetic field generating device closer to the reaction vessel position, It is possible to improve the washing separation efficiency while reducing the adsorption time of paramagnetic particles. The washing mechanism includes a liquid suction and liquid injection device for sucking unbound components in the reaction container and injecting a washing buffer solution into the reaction container after suction. The liquid suction device includes a liquid suction part suitable for liquid suction, such as a liquid suction needle, a liquid suction tube or a liquid suction nozzle, and the like, and the liquid suction part is disposed on the top of the reaction unit, and advances to the reaction container on the reaction container position by a driving mechanism. While doing this, unbound components in the reaction vessel can be introduced. The liquid injection device includes a suitable liquid injection part such as a liquid injection needle, tube, nozzle, etc., and the liquid injection part is also mounted on the upper part of the reaction vessel position of the reaction unit to inject the washing buffer solution into the suction-completed reaction container. Each washing includes a first liquid incorporation process and a first washing buffer injection process, and is generally washed three times or four times, that is, washing three times or four times, but is not limited thereto. For less residue and more thorough cleaning, install a mixer in the liquid injection position to mix uniformly, or use the impact force generated during liquid injection to reproduce paramagnetic particles in the washing buffer during or after injection of the washing buffer. Turbid and evenly disperse. After the reaction vessel is transferred to the reaction vessel washing and separating unit 30 by the reaction tray of the reaction unit, the washing and separating unit 30 cleans and separates the reaction vessel. In addition, in order to simplify the mechanism, the washing and separating unit 30 may further include a signal reagent addition mechanism for adding all or part of the signal reagent to the reaction vessel after the reaction vessel is washed and separated. For example, all of the first signal reagent and the second signal reagent may be added, or only the first signal reagent may be added, and the remaining signal reagents may be injected during the measurement period. Accordingly, it is possible to reduce the volume of the mechanism and reduce the cost by sufficiently utilizing the function of the washing and separating mechanism. According to the above description, the washing and separating device 30 is mounted around the reaction tray of the reaction unit or on the upper portion of the reaction tray, by directly washing and separating the reaction vessel mounted on the reaction tray of the reaction unit, or an independent washing/separating tray or There is no need to install an independent washing separation rotating device such as a washing separation track, etc., simplifying the structure of the parts and the entire device to make the structure of the entire device more compact, reducing the cost, and the reaction vessel with an independent washing separation device. There is no need to move between reaction units, thereby making the control process of the immune analyzer simpler and more efficient, improving processing efficiency and reliability.

The measuring device 40 measures a signal in the reaction vessel. The signal is an electrical signal, a fluorescent signal, or a weak chemiluminescent signal generated after adding a signaling reagent in the reaction vessel. The measuring device 40 may include a weak light meter photomultiplier tube (PMT) or other sensitive photoelectric sensing element, and may convert the measured optical signal into an electrical signal and transmit it to the control center. In addition, in order to improve measurement efficiency and ensure measurement consistency, the measurement device 40 may further include an optical device such as optical signal collection and correction. Taking a weak chemiluminescent signal as an example, in order to avoid interference from ambient light rays, the measuring device 40 of the present invention is mounted on the reaction unit to measure the reaction signal on the reaction vessel position of the reaction unit. Thus, through full use of the reaction vessel position on the reaction apparatus, the entire apparatus is made more compact and costs are reduced.

Depending on the measurement conditions, the reaction vessel requiring cultivation first is incubated for a certain period of time in the culture position of the inner three cycles (11a, 11b, 11c) or after the cultivation is completed, it is transferred to the outer cycle of the reaction tray for washing separation The measurement is performed or transferred to a position other than the reaction culture device 100 to perform the corresponding operation. The reaction vessel may be transferred to the outer cycle 11d to perform washing separation after completing the culture in the inner three cycles 11a, 11b, 11c, or the inner three cycles 11a, 11b, 11c ) After performing the cultivation for a certain period of time, for example, after performing the cultivation of most of the time, it is transferred to the outer cycle 11d, and the cultivation of the remaining time is completed between the reaction tray being transferred to the magnetic separation device. In the first implementation method, the outer cycle 11d does not require a separate reaction vessel position for cultivation, so the size of the reaction tray is smaller and the cost can be reduced. In the second implementation method, for example, when the reaction vessel to be measured is incubated for 25 minutes, the incubation for most of the time, such as 24 minutes, is first performed on one or more of the inner three cycles (11a, 11b, 11c). Can, and is transferred to the outer cycle (11d), the remaining 1 minute incubation is completed before being transferred to the washing separation device. In this method, since some culture functions are performed on the outer cycle, the number of culture positions on the inner three cycles can be appropriately reduced, balance the quantity of the reaction vessel positions on the inner and outer cycles, and the size of the reaction tray To optimize and make the most of the inner space of the reaction tray.

It can be sufficiently understood by those skilled in the art that the reaction culture process and steps of this embodiment are similar to those of the first embodiment. Likewise, with reference to FIGS. 3 to 5, as an example of measurement in which culture was performed for 5.8 minutes, the reaction culture process and steps of the reaction culture apparatus 100 will be briefly described.

Step 200 is the step of bringing the mobile unit into the reaction vessel culture position. During the stop time (C ₁ -C ₂ hours) at which the reaction tray 11 stops rotating, the moving unit 20 moves the reaction vessel containing the reactants to the incubation position on the absolute position (1), and selects any of the three cycles. It should be located on one of the above. For example, it is possible to select the culture position on the inner cycle 11a at the absolute position 1.

Step 201 is a step of incubating the reaction vessel for t _{1 hour.} The reaction vessel is rotated counterclockwise by a predetermined angle (θ) of 12° every 24 seconds in one cycle (T) by the reaction tray 11, and moves forward by one reaction vessel position. After passing through 12 cycles T, the reaction vessel is rotated by a total angle (Ω) 144° by a rotating device in the culture position to be positioned on the absolute position 13, and the incubation time (t ₁ ) accordingly is ( Ω/θ)T+C ₀ =4.8+0.2=5min. In this example, the constant C ₀ is 0.2 minutes.

Step 202 is a step of removing the reaction vessel from the culture position by the mobile unit. After the incubation time (t ₁ ), the mobile unit 20 is in the culture position on the outer cycle 11d located at the absolute position 13 within the _{stop time (C 3} -C _{4 hours) at which the reaction tray 11 stops rotating.} The reaction vessel containing the reactants was taken out.

During the incubation time (t ₁ ) or after the incubation is completed, if washing separation and measurement are required in the measurement process, the reaction vessel is positioned on the outer cycle 11d at the absolute position 15 by the mobile unit 20 Is moved to. _{Depending on the measurement conditions, the reaction vessel is incubated at a time (t 0} ) (t ₀ ≥0) on the outer cycle (11d) before being transferred to the washing and separating device 30, and the reaction vessel is in a position other than the culture position on the rotating device. Time), or it may be directly transferred to the washing/separating device 30 without continuing culture. In this embodiment, the moving unit 20 moves the reaction vessel to the reaction vessel position of the outer cycle 11d on the absolute position 15, and after two periods of time, the reaction vessel is a washing separation device ( 30), and at this time, the incubation time (t ₀ ) on the outer cycle 11d is 48 seconds. Therefore, the total culture time (t) performed in the automatic reaction culture apparatus 100 of this embodiment is t ₁ +t ₀ =5.8 minutes. After completion of the culture, the reaction vessel is transferred to a washing and separating device according to the rotation of the reaction tray 11, and multi-stage washing and separating is performed by the washing and separating device 30. While being transferred to the measuring device 40 according to the rotation of the reaction tray 11, the measuring device 40 measures a signal in the reaction vessel. In another embodiment, after the reaction vessel is removed from the culture position, the culture is not continued before entering the washing separation device 30, and the total culture time (t) performed at this time is t ₁ =5 minutes.

For delayed one-step and two-step methods requiring two cultures, it will be understood by those skilled in the art that the incubation time of this example can be varied according to a similar process and method.

According to the above, in this embodiment, the variable incubation time (t ₁ ) that can be performed in the culture position is (Ω/θ)T+C _0, where Ω is the reaction vessel rotated by the rotating device in the culture position. Is the total angle, Ω is an integer multiple of θ, and C ₀ is a constant equal to or less than T. In particular, in this embodiment, for a longer incubation time, the total angle (Ω) at which the reaction vessel is rotated according to the rotating device in the culture position on the reaction tray includes a value greater than 360°. In other words, the variable incubation time (t ₁ ) includes a value greater than (360°/θ)T. Therefore, the reaction vessel moves forward while rotating by the reaction tray on the culture position, and the mobile unit can freely change the incubation time by bringing the reaction vessel into the culture position on the reaction tray or taking it out from the culture position at different positions. .

Referring to Fig. 7, a third embodiment according to the present invention is shown. The main difference in this embodiment compared to the second embodiment is the moving unit 20 and the washing and separating device 30. In this embodiment, the moving unit 20 can move two-dimensionally as one, horizontally in a vertical direction and vertically in a vertical direction, thereby making the entire device more compact and cost reduction. The moving unit 20 includes a rail 20b in the Y direction, a moving robot arm 20a in the Y direction, and a vertical movement mechanism, a mechanical finger (not shown), and the like. The movement unit 20 can move the mechanical finger along the horizontal direction in the Y direction, and the horizontal movement path is denoted by 26. In other words, the reaction vessel position located at the absolute position (1) on the reaction tray 11 is within the horizontal movement range of the mobile unit 20, whereby the mobile unit 20 places the reaction vessel at the absolute position (1). It can be brought into or out of the container position. In this embodiment, the washing and separating device 30 is installed on the inner cycle of the reaction unit, making the washing and separating device more compact and reducing adverse effects such as temperature change and interference from ambient light caused by the washing and separating device. have.

In this embodiment, the culture function is mainly performed at the reaction vessel position on the two cycles 11b and 11c located in the middle, the washing separation function is mainly performed at the reaction vessel position on the inner cycle 11a, and the outer cycle 11d ) Mainly performs the measurement function at the position of the reaction vessel. Of course, the reaction vessel position on the inner cycle 11a may partially perform a culture function in the process of transferring the reaction vessel to the washing and separating device 30. In the measurement process, the reaction vessel to be cultured is first moved on one of two cycles (11b, 11c) located in the middle by the transfer unit 20, and after completion of culture or after incubation for a certain period of time, if washing and separation are required It is moved on the two cycles 11b and 11c positioned in the middle by the moving unit 20, and is moved on the inner cycle 11a again, and is multi-stage through the washing and separating device 30 according to the rotation of the reaction tray. After performing the washing separation, it is carried out in the inner cycle d by the moving unit 20.

It can be understood by those skilled in the art that the reaction culture process and steps of this embodiment are the same as or similar to those of the second embodiment, and the reaction culture process and procedure may refer to FIGS. 3 to 5, and incubation for 12.6 minutes Taking the measurement as an example, the reaction culture process and steps of the reaction culture apparatus 100 will be briefly described.

Step 200 is the step of bringing the reaction vessel into the culture position by the mobile unit. During the stop time (C ₁ -C ₂ hours) when the reaction tray 11 stops rotating, the moving unit 20 moves the reaction vessel containing the reactants to the culture position on the absolute position (1), It is placed on any one of the cycles 11b and 11c. For example, it can be selected as the culture position on the absolute position (1) and the intermediate cycle (11c).

Step 201 is a step of incubating the reaction vessel for t _{1 hour.} The reaction vessel is rotated counterclockwise by a predetermined angle (θ) of 12° every 24 seconds in one cycle (T) by the reaction tray 11, and moves forward by one reaction vessel position. After passing through 30 cycles T, the reaction vessel is rotated by a total angle (Ω) 360° by a rotating device in the culture position to be positioned on the absolute position (1), and the incubation time (t ₁ ) accordingly is ( Ω/θ)T+C ₀ =12+0.2=12.2min. In this example, the constant C ₀ is 0.2 minutes.

Step 202 is a step of removing the reaction vessel from the culture position by the mobile unit. After the incubation time (t ₁ ), the mobile unit 20 is in the incubation position on the intermediate cycle 11c located at the absolute position 13 during the _{stop time (C 3} -C _{4 hours) at which the reaction tray 11 stops rotating.} The reaction vessel containing the reactants was taken out.

During the reaction time (t ₁ ) or after the incubation is completed, if washing separation and measurement are required in the measurement process, the reaction vessel is positioned on the inner cycle 11a at the absolute position (1) by the mobile unit 20. After moving to and performing washing separation, after passing through 30 cycles (T), the measurement is carried out by moving from the absolute position (1) to the outer cycle (11d) again. Depending on the measurement conditions, the reaction vessel is placed on the inner cycle for a period of time (t ₀ ) (t ₀ ≥ 0, the incubation time in a position other than the incubation position on the rotating device when the reaction vessel is incubated) before being transferred to the washing separation device 30 The cultivation may be continued or may be directly transferred to the washing separation device 30 without continuing cultivation. In this embodiment, the moving unit 20 moves the reaction vessel from the absolute position 1 to the culture position of the inner cycle 11a, and after one time period, the reaction vessel is washed and separated by the device 30 ), and the incubation time (t ₀ ) on the inner cycle 11a is 24 seconds. Therefore, the total incubation time (t) performed in this example is t ₁ +t ₀ =12.6 minutes. After completion of the culture, the reaction vessel is transferred to the washing and separating device 30 according to the rotation of the reaction tray, and multi-stage washing and separating is performed by the washing and separating device 30. When the reaction vessel is returned to the reaction vessel position on the inner cycle 11a from the absolute position 1 after completion of washing and separation, the outer cycle ( It moves again to 11d) and measures, and the signal in the reaction vessel is measured by the measuring device 40 while passing through the measuring device 40 by rotation of the reaction tray. In another embodiment, after the reaction vessel is removed from the culture position, the culture is not continued before entering the washing separation device 30, and the total culture time (t) performed at this time is t ₁ =12.2 minutes.

Regarding the delayed one-step and two-step method requiring two cultures, it will be understood by those skilled in the art that this embodiment allows the culture time to be changed each time according to the culture process and procedure.

According to the above, in this embodiment, the variable incubation time (t ₁ ) that can be performed in the culture position is (Ω/θ)T+C _0, where Ω is the reaction vessel rotated by the rotating device in the culture position. Is the total angle, Ω is an integer multiple of θ, and C ₀ is a constant equal to or less than T. In particular, in this embodiment, in order to carry out 2 or more incubation times, the total angle (Ω) at which the reaction vessel is rotated according to the rotating device in the culture position on the reaction tray includes a value greater than 360°. In other words, the variable incubation time (t ₁ ) includes a value greater than (360°/θ)T. Thus, the reaction vessel is rotated and advanced forward by the reaction tray on the culture position, thereby making it possible to freely change the incubation time.

In an embodiment of the present invention, an immunoassay is further provided, and a reaction culture device is mounted on the immunoassay.

An embodiment of the present invention further provides a reaction culture method, the method

A carrying step of transferring the reaction vessel containing the reactants to the culture position of the reaction unit by the moving unit;

A culture step in which the reaction vessel is moved forward by a predetermined angle (θ) at intervals of a predetermined time (T) by a rotating device in the culture position and cultured for a variable culture time [t ₁ =(Ω/θ)T], wherein , Ω is the total angle at which the reaction vessel is rotated by the rotating device in the culture position, and Ω is an integer multiple of θ, a culturing step;

After the incubation time (t ₁ ), it includes a carrying out step of carrying out the reaction vessel from the culture position of the reaction unit by a mobile unit.

In addition, the total angle (Ω) in which the reaction vessel is rotated by the rotating device includes at least one value greater than 360°, that is, the variable incubation time (t ₁ ) is greater than at least one (360°/θ)T Includes large values. The total incubation time (t) according to the reaction culture method is t ₁ +t _0, where t ₀ is 0 or more, and the reaction vessel is incubation time at a position other than the incubation position of the rotating device.

The reaction culture apparatus of the present invention moves the reaction vessel by a predetermined angle (θ) at intervals of a predetermined time (T), and the moving unit unloads the reaction vessel from the culture position according to the _{variable culture time (t 1 ).} In the present invention, in addition to implementing freely variable incubation time, it is possible to control simply and efficiently, washing, separating and/or measuring simultaneously on the reaction culture device, so that the immunoassay is simple, reliable, compact and cost-saving. This effectively solves the problems of the prior art in which the control for implementing a variable incubation time is complicated, the reliability is low, high-speed automation is difficult to execute, and the washing, separation and/or measurement cannot be performed simultaneously. do.

The technical features or operational steps described in the embodiments of the present invention may be combined in any suitable manner. Those skilled in the art should understand that the order of steps or actions in the methods presented in the embodiments of the present invention may be changed. Accordingly, unless a separate description requires a certain order, any order in the accompanying drawings or detailed description is for illustration only and is not an essential order.

Various steps that can be implemented as machine-executable instructions executable by a general purpose or dedicated computer (or other electronic device) may be included in various embodiments of the present invention. Optionally, these steps may be performed jointly by hardware, software, and/or firmware, or a hardware element containing specific logic circuitry to perform these steps.

Although the present invention has been described by the above specific embodiments, the present invention is not limited to the above specific embodiments. Those skilled in the art should understand that various modifications, substitutions and changes of equivalents made without departing from the spirit of the present invention are within the scope of the present invention. In addition, the aforementioned various "one embodiment", "this embodiment" and the like represent different embodiments, and of course, all or part of them may be combined in one embodiment.

The above-described embodiments are only for describing some embodiments of the present invention, and the description is more specific and detailed, but is not construed as limiting the scope of the present invention. Those skilled in the art will understand that various changes and modifications made without departing from the spirit and scope of the present invention fall within the scope of the claims of the present invention. Therefore, the scope of the invention is determined by the appended claims.

Claims (10)

A reaction unit for cultivation equipped with a reaction vessel;
A moving unit carrying the reaction vessel into or out of the reaction unit; And
Washing and separating device for washing and separating the reaction vessel
As a reaction culture device comprising a,
The reaction unit includes a rotation device, a culture position is installed on the rotation device, the culture position is rotated by a predetermined angle (θ) by the rotation device at intervals of a predetermined time (T) to move forward, and the The rotating device is a reaction tray,
The movement unit includes a grip and release mechanism, and a horizontal movement arm, the grip and release mechanism can hold or lower the reaction vessel, and the horizontal movement arm adjusts the grip and release mechanism to at least one of an X-direction and a Y-direction. Horizontally move along one, and the moving unit removes the reaction vessel from the culture position according to the _{incubation time (t 1 ),}
The washing and separating device is mounted around the reaction tray of the reaction unit or above the reaction tray, and the reaction vessel is directly washed and separated from the reaction tray of the reaction unit. The method of claim 1,
The incubation time (t ₁ ) is (Ω/θ)T+C _0, where Ω is the total angle at which the reaction vessel is rotated by the rotating device at the culture position, and Ω is an integer multiple of θ, The _{reaction culture apparatus, characterized in that C 0} is the same as T or a constant less than T. The method of claim 2,
The total angle (Ω) at which the reaction vessel is rotated by the rotating device in the culture position includes a value greater than at least one 360°, that is, the variable incubation time (t ₁ ) is at least one (360°/ θ) A reaction culture apparatus comprising a value greater than T. The method of claim 2,
The total incubation time (t) that the rotating device can perform is t ₁ +t ₀ , wherein t ₀ is greater than or equal to 0, and the reaction vessel is an incubation time at a position other than the incubation position of the rotating device. Reaction culture apparatus. The method of claim 1,
The reaction culture apparatus, characterized in that the culture position is distributed on at least one circle having a center of the reaction tray centrifuged. The immune analyzer, characterized in that the reaction culture device according to any one of claims 1 to 5 is mounted on the immune analyzer. A carrying step of transferring the reaction vessel containing the reactants to the culture position of the reaction unit by the moving unit;
As a culture step of rotating the reaction vessel in the culture position by a predetermined angle (θ) at intervals of a predetermined time (T) by a rotating device, and incubating for a variable culture time [t ₁ =(Ω/θ)T], In this case, Ω is the total angle at which the reaction vessel is rotated by the rotating device in the culture position, and Ω is an integer multiple of θ, a culturing step; And
After the lapse of the variable cultivation time (t ₁ ), the carrying out step of the mobile unit taking out the reaction vessel from the cultivation position of the reaction unit
As a reaction culture method comprising a,
The movement unit includes a grip and release mechanism, and a horizontal movement arm, the grip and release mechanism can hold or lower the reaction vessel, and the horizontal movement arm adjusts the grip and release mechanism to one of the X and Y directions. Characterized in that horizontal movement along at least one, reaction culture method. The method of claim 7,
In the reaction vessel, the total angle (Ω) rotated by the rotating device includes a value greater than at least one 360°, that is, the variable incubation time (t ₁ ) is at least one (360°/θ)T Characterized in that it comprises a larger value, reaction culture method. The method of claim 7,
The total incubation time (t) performed by the reaction incubation method is t ₁ +t _0, where t ₀ is 0 or more, and the reaction vessel is incubation time at a position other than the incubation position of the rotating device. Characterized in that, the reaction culture method. delete

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